AT1 and glutamatergic receptors in paraventricular nucleus support blood pressure during water deprivation

Korrina L. Freeman, Virginia Brooks

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Abstract

Water deprivation activates sympathoexcitatory neurons in the paraventricular nucleus (PVN); however, the neurotransmitters that mediate this activation are unknown. To test the hypothesis that ANG II and glutamate are involved, effects on blood pressure (BP) of bilateral PVN microinjections of ANG II type 1 receptor (AT1R) antagonists, candesartan and valsartan, or the ionotropic glutamate receptor antagonist, kynurenate, were determined in urethane-anesthetized water-deprived and water-replete male rats. Because PVN may activate sympathetic neurons via the rostral ventrolateral medulla (RVLM) and because PVN disinhibition increases sympathetic activity in part via increased drive of AT1R in the RVLM, candesartan was also bilaterally microinjected into the RVLM. Total blockade of the PVN with bilateral microinjections of muscimol, a GABAA agonist, decreased BP more (P <0.05) in water-deprived (-29 ± 8 mmHg) than in water-replete (-7 ± 2 mmHg) rats, verifying that the PVN is required for BP maintenance during water deprivation. PVN candesartan slowly lowered BP by 7 ± 1 mmHg (P <0.05). In water-replete rats, however, candesartan did not alter BP (1 ± 1 mmHg). Valsartan also produced a slowly developing decrease in arterial pressure (-6 ± 1 mmHg; P <0.05) in water-deprived but not in water-replete (-1 ± 1 mmHg) rats. In water-deprived rats, PVN kynurenate rapidly decreased BP (-19 ± 3 mmHg), and the response was greater (P <0.05) than in water-replete rats (-4 ± 1 mmHg). Finally, as in PVN, candesartan in RVLM slowly decreased BP in water-deprived (-8 ± 1 mmHg; P <0.05) but not in water-replete (-3 ± 1 mmHg) rats. These data suggest that activation of AT1 and glutamate receptors in PVN, as well as of AT1R in RVLM, contributes to BP maintenance during water deprivation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume292
Issue number4
DOIs
Publication statusPublished - Apr 2007

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Keywords

  • Angiotensin II
  • Candesartan
  • Glutamate
  • Rostral ventrolateral medulla
  • Valsartan

ASJC Scopus subject areas

  • Physiology

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